In humans, herpes simplex virus type 1 (HSV-1) causes keratitis and often causes recurrent disease and eventually scarring and decreased visual acuity. In fact, herpes keratitis is the leading cause of corneal blindness in the United States today. The corneal nerves are involved in herpes keratitis in several ways. Corneal nerves are probably involved directly in herpetic keratitis, since studies have shown that patients with HSV-1 keratitis have decreased corneal sensitivity. The virus also probably ascends the corneal nerves and becomes latent in the trigeminal ganglion and then, for unknown reasons, is triggered to descend the nerves to the eye, causing recurrent disease. Recent research has established the normal three-dimensional organization and density of rabbit corneal nerves by means of a gold chloride staining and light microscopy. These techniques will be used here to study HSV-1 keratitis in rabbit corneas. The primary purpose of this pilot study will be to determine quantitatively the type and extent of nerve alterations in rabbit corneas infected with HSV-1. To do this, rabbit eyes with acute, healed, and recurrent keratitis will be examined. These experiments will be repeated with several distinct strains of HSV-1, each known to give a different type of clinical keratitis in rabbits, to determine whether there is strain-specific nerve alteration and, if there is, its relationship to recurrent disease. A thymidine kinase negative strain will also be evaluated to see whether the apparent inability of this strain to establish latency is related to the type and/or extent of nerve damage. This project should for the first time give us basic, quantitative information on corneal epithelial nerve alterations in herpetic keratitis, and will, if decreased nerve density is found as expected, establish the cause of the associated decreased sensitivity. Additionally, a finding that the clinically observed strain-specific effects of different HSV-1 strains is associated with specific nerve alterations will add convincing evidence that strain specificity, rather than host factors, is the main determinant of the type and extent of clinical disease. Ultimately, the long-term objective of this pilot project and further research on the role of peripheral nerves in HSV-1 keratitis is the development of new drug treatments, acting upon the ocular nerves, to control herpetic keratitis.